Project Summary/Abstract While significant progress has been made in reducing cigarette smoking among adolescents, the advent of electronic cigarettes and vaping devices threatens to undo this progress. While e-cigarettes have potential as harm reduction tools for adult smokers, they have become the most commonly-used tobacco product among adolescents. In 2018, the Food and Drug Administration (FDA) declared e-cigarette use among adolescents an ?epidemic? after observing dramatic increases in usage among this population since 2017. Evidence-based health communication approaches can strengthen young people?s commitment to avoid vaping, and thus prevent e-cigarette use and nicotine addiction. However, little research exists to provide a basis for effective communication efforts for e-cigarette prevention. We propose 3 Aims to significantly advance the science of how to communicate about e-cigarettes in ways that prevent use. For Aim 1, we will identify promising ways to communicate with adolescents to prevent e-cigarette use. We will achieve this by: 1) identifying promising prevention message themes (i.e., industry targeting, social norms, addiction) targeted to adolescents (ages 13- 17); 2) vetting these themes with the study team, expert consultants, and a teen advisory panel; and 3) conducting focus groups to examine adolescents? responses to the e-cigarette prevention message themes. For Aim 2, we will develop a set of e-cigarette prevention messages that reduce adolescents? inclination to try or use e-cigarettes. We will achieve this by: 1) developing 10 e-cigarette prevention messages based on the chosen theme(s) from Aim 1 and conducting 30 cognitive interviews to refine the messages; and 2) conducting a nationally representative study to examine the perceived effectiveness of the e-cigarette prevention messages in discouraging e-cigarette use. Based on the results, we will select 5 messages to carry forward to Aim 3?s randomized controlled trial (RCT). For Aim 3, we will evaluate whether evidence-based e-cigarette prevention messages reduce at-risk adolescents? willingness to use e-cigarettes (primary outcome) and e- cigarette use behavior (secondary outcome). We will conduct a 2-arm (intervention, attention control), 3-week RCT with 506 adolescents, with a 3-month follow up. Study participants will receive daily messages sent to their mobile phones via text message (i.e., multimedia message service) for 20 days. Other secondary outcomes are cognitive elaboration, negative affect, e-cigarette beliefs, and social interactions. We will also examine whether e-cigarette prevention messages have unintended consequences (i.e., increasing willingness to smoke cigarettes). This research is responsive to funding announcement PAR-18-847, which seeks population-based, applied prevention research on e-cigarettes among vulnerable populations (e.g., youth). Our work will address a critical gap in tobacco control research by developing effective communications that strengthen adolescents? commitment to avoid e-cigarettes and reduce e-cigarette use, thereby informing local, state, and national efforts to prevent e-cigarette use and nicotine addiction among adolescents.